Recessive Dystrophic Epidermolysis Bullosa (RDEB), a genodermatosis caused by mutations on COL7A1 gene, encoding the anchoring fibril-forming type VII collagen, is characterized by scarring and mucocutaneous blistering. We studied two sisters with the same Spanish recurrent mutation in COL7A1 (c6527insC), but with markedly discordant phenotypes. Based on clinical manifestations, the less affected patient displayed enhanced skin adherence and reduced fibrosis, in comparison with her sister, that shares the consensus phenotype with a large cohort of Spanish severe generalized RDEB patients bearing same mutation. Fibroblasts from the two sisters and from 7 other isogenic RDEB patients were analyzed for their global expression profile by RNA-Seq. The results revealed a set of 339 genes, associated in large part to the extracellular matrix, that are differentially expressed between the mild patient and all other typical RDEB patients. A protein-protein interaction network analysis of these genes revealed a cluster of 11 genes related to basement membrane adhesion, extracellular matrix stability, and fibrosis. These results highlight new molecular mechanisms involved in RDEB and may open new possibilities for therapeutic intervention.

Comparative transcriptomic analysis of fibroblasts from two sisters with discordant severe generalized recessive dystrophic epidermolysis bullosa phenotype reveals new molecular markers associated with disease severity.